On July 4, 2014 Roche reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved alectinib for the treatment of people living with non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase fusion gene-positive (ALK+) (Press release Hoffmann-La Roche, JUL 4, 2014, View Source [SID:1234500613]). The approval was based on results from a Japanese Phase I/II clinical study (AF-001JP) for people whose tumors were advanced, recurrent or could not be removed completely through surgery (unresectable).

“The approval of alectinib, a treatment specifically targeted to ALK+ lung cancer, in Japan is great news for people living with this difficult to treat disease,” said Sandra Horning MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Another interesting aspect of alectinib is that based on early studies it may also work in people living with tumors that have spread to the brain, a difficult area to reach with current medicines. Our research will continue in this area.”

Alectinib is expected to be made available in Japan later this year. Alectinib was also granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) in June 2013 for patients with ALK+ NSCLC who progressed on crizotinib. BTD is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible.

Global pivotal studies are currently ongoing which will further inform on the clinical value of alectinib in this disease setting as well as in treatment-naïve patients. The results of these studies will be used in future regulatory submissions in the US and in Europe.

About the Japanese Phase I/II study (AF-001JP)
This trial was conducted in 13 medical institutions in ALK fusion gene positive recurrent or advanced non-small cell lung cancer patients with a treatment history of one or more chemotherapy regimens.

The trial consisted of two phases: Phase I that evaluated safety, tolerability, pharmacokinetic parameters and recommended dose (24 patients), and a Phase II part that evaluated the efficacy and safety of the recommended dose (46 patients). The primary endpoint was response rate.

Japanese Phase I/II study (AF-001JP) results
The Phase I part of the study determined a recommended dose of 300 mg twice daily. No dose limiting toxicity was observed.

The Phase II portion of the study was conducted using the recommended dose, and demonstrated a response rate of 93.5% (43/46 patients; 95%CI: 82.1-98.6%).
– 14 patients entered the study with Central Nervous System (CNS) metastases1
– 9 of the 14 patients remained in the study without CNS or systemic progression for more than 12 months1
Progression Free Survival (PFS) at 12 months was measured as 83% (95% CI: 68-92%)1
There were no treatment-related deaths and/or grade 4 or higher serious adverse reactions assessed according to CTCAE (Common Terminology Criteria for Adverse Events) defined by the Japan Clinical Oncology Group. The most frequently observed grade 3 or higher adverse reaction was neutropenia, and the incidence of the adverse event was 4 out of 58 patients (6.9%) who were treated with 300 mg twice daily, the approved dose